Non-alkylating agents-induced gonadotoxicity in pre-pubertal males: Insights on the clinical and pre-clinical front.

Whilst chemotherapy regimens have proven to be more successful for pediatric cancer patients over the years, their influence on long-term side effects is relatively poorly understood. One of the possible targets is the gonads, with gonadotoxic agents representing those that threaten the patient's ability to have children post surviving the primary disease treatment. Many risk stratification guidelines have categorized these agents based on the severity of their effect on the pre-pubertal testis.

Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.

Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic 'fetal' and WNT-high 'embryonal', displaying divergent WNT signaling patterns.

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100.

Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis.